6-30952347-G-T

Variant names:

• chr6-30952347-G-T
• rs3132580
• NM_080870.4:c.3883G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080870.4(MUCL3):​c.3883G>T​(p.Glu1295*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MUCL3 NM_080870.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 54 publications found

Genes affected

MUCL3 (HGNC:21666): (mucin like 3) Predicted to be located in cytoplasm and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

HCG21 (HGNC:31335): (HLA complex group 21)

SFTA2 (HGNC:18386): (surfactant associated 2) Predicted to be located in Golgi apparatus; extracellular region; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL3	NM_080870.4	c.3883G>T	p.Glu1295*	stop_gained	Exon 2 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1	n.256+15C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUCL3	ENST00000462446.6	c.3883G>T	p.Glu1295*	stop_gained	Exon 2 of 3	5	NM_080870.4	ENSP00000417182.1
HCG21	ENST00000419481.1	n.224+720C>A		intron_variant	Intron 2 of 2	3
SFTA2	ENST00000634371.2	n.513+15C>A		intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Benign	0.90
Eigen	Benign	-0.64
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
PhyloP100		-0.99
Vest4		0.025, 0.092
GERP RS		-7.2
Mutation Taster		=101/99	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3132580; hg19: chr6-30920124;